rs137852557
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 11P and 4B. PS1PM1PP3_StrongPP5BS2
The NM_000451.4(SHOX):c.502C>T(p.Arg168Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin ClinVar.
Frequency
Consequence
NM_000451.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHOX | NM_000451.4 | c.502C>T | p.Arg168Trp | missense_variant | 3/5 | ENST00000686671.1 | |
SHOX | NM_006883.2 | c.502C>T | p.Arg168Trp | missense_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHOX | ENST00000686671.1 | c.502C>T | p.Arg168Trp | missense_variant | 3/5 | NM_000451.4 | P1 | ||
SHOX | ENST00000381575.6 | c.502C>T | p.Arg168Trp | missense_variant | 3/5 | 1 | |||
SHOX | ENST00000381578.6 | c.502C>T | p.Arg168Trp | missense_variant | 4/6 | 5 | P1 | ||
SHOX | ENST00000334060.8 | c.502C>T | p.Arg168Trp | missense_variant | 4/6 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251180Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135744
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461670Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727144
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Leri-Weill dyschondrosteosis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2002 | - - |
Langer mesomelic dysplasia syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2002 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at